Mechanistic Strategies and Programmable Translational Applications of Biomaterials for Tendon-to-Bone Healing

Tendon-to-bone healing (TBH) presents a major challenge to sports medicine and orthopedics. Conventional surgical approaches can restore structural continuity but rarely reestablish the native graded interface or achieve long-term mechanical stability, which frequently results in fibrotic repair and functional deficits. Biomaterials offer unique advantages due to their programmability and multifunctionality, enabling spatial and temporal regulation of immune and mechanical microenvironments through mechanotransduction-associated pathways, including integrin/focal adhesion kinase (FAK), Yes-associated protein (YAP)/transcriptional co-activator with postsynaptic density protein 95, discs large protein, and zonula occludens-1 (PDZ)-binding motif (TAZ), and mitogen-activated protein kinase (MAPK) signaling, thereby modulating cellular behavior, interface remodeling, and functional tissue integration. These properties support the transition from simple structural reattachment to functional integration. Recent advances have shifted the field from material-type-driven descriptions to mechanism-oriented design principles such as phase-specific regulation, immuno–mechanical coupling, mineralization-gradient engineering, and manufacturability considerations. Future developments should prioritize causal links between material properties and biological responses, unified evaluation frameworks, intelligent and digital design, and early integration of clinical, regulatory, and manufacturing requirements. Programmable interface biomaterials may thereby accelerate the transition of tendon–bone interface repair from structural reattachment to precision-guided functional regeneration.